# Mechanisms underlying the reduction in alcohol intake in response to low intensity targeting of the reward circuit

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2023 · $367,242

## Abstract

Alcohol use disorder (AUD) remains a major issue in the United States (US) despite the various laws, campaigns,
and preventative efforts. Alcohol is by far the most commonly-abused drug across the lifespan. According to
2015 data from The National Survey on Drug Use and Health, there are currently 138 million alcohol users in
the US, with almost half of drinkers reporting problem drinking (binge or heavy alcohol consumption), and 15.7
million reporting an AUD. A host of pharmaceutical targets have been identified, but treatment efficacy and
abstinence rates both remain low due to factors such as cost, negative physiological effects, and requirements
of long-term commitment to treatment. Thus, new directions for addiction treatment are needed. In one such
direction, recent advances in ultrasound technology have enabled the non-invasive modulation of deep brain
systems such as the reward circuit. We propose a novel combination of low intensity focused ultrasound (LIFU)
with photoacoustic tomography (PAT) localization to modify the activity of the two primary components of the
reward system, the ventral tegmental area and nucleus accumbens. Our preliminary work has demonstrated that
this approach reduces alcohol intake and preference when administered once daily in either region. Thus, in the
proposed studies, we will examine the mechanisms by which LIFU reduces alcohol intake, the longevity of this
effect, and potential side effects of this treatment on the brain. We will first optimize our protocol for maximum
efficacy in the deep brain regions of the reward circuit. Next, we will assess a variety of behaviors related to
affect and to alcohol-seeking in order to identify the neurological processes on which LIFU is exerting its effects.
Finally, we will assess the molecular effects in the brain following LIFU treatment, in order to identify those
neuronal changes that may explain the behavioral shifts, and to determine whether there are any adverse effects
on neuronal function following chronic LIFU treatment. For these studies, we will use male and female crossed
high-alcohol-preferring mice, in order to identify whether there are sex-dependent differences in the effects of
LIFU on alcohol-seeking, or in the neuronal effects of LIFU. These studies will provide an essential foundation
of knowledge for the use of LIFU to reduce AUD, and will open the door to a wide spectrum of further studies
examining other substance use disorders, and use of LIFU in traditionally difficult to treat populations, such as
adolescents, or for disorders commonly comorbid with AUD, such as sleep disorders.

## Key facts

- **NIH application ID:** 10733248
- **Project number:** 1R01AA030572-01A1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Danielle Gulick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $367,242
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10733248

## Citation

> US National Institutes of Health, RePORTER application 10733248, Mechanisms underlying the reduction in alcohol intake in response to low intensity targeting of the reward circuit (1R01AA030572-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10733248. Licensed CC0.

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